Tuberculosis is a chronic infectious disease caused by infection with Mycobacterium tuberculosis or other Mycobacterium species. Tuberculosis is one of major diseases in developing countries, as well as an increasing problem in developed countries, with about 8 million new patients and 3 million deaths each year. The infection may be asymptomatic for a considerable period of time. However, tuberculosis is most commonly manifested as an acute inflammation of the lungs, resulting in fever and non-productive cough. Moreover, if not treated, serious complications and death are typically caused.
Tuberculosis can be treated using antibiotic therapy over a long period of time, but such treatment is not sufficient to prevent the spread of tuberculosis. Infected individuals may be asymptomatic, but contagious, for a certain period of time. In addition, patient behavior is difficult to monitor although the treatment regimen is strictly followed. Some patients fail to complete the course of treatment, which may result in ineffective treatment and the development of drug resistance. Even after completion of the whole course of treatment, infection with Mycobacterium tuberculosis cannot be rooted out from infected individuals but still remains a latent infection that can be reactivated.
In order to control the spread of tuberculosis, effective vaccination and accurate early diagnosis of the disease are most important. Currently, vaccination with live bacteria is the most efficient way for inducing protective immunity. The most common Mycobacterium used for this purpose is Bacillus Calmette-Guerin (BCG), an avirulent strain of M. bovis. However, the stability and efficacy of BCG is an issue of controversy, and some countries, such as the US, do not vaccinate the general public with this agent. Thus, studies continue on a technique for preventing tuberculosis infection that is excellent in stability and efficacy, compared with previous techniques.
Diagnosis of tuberculosis is typically achieved using a skin test, which involves intradermal exposure to tuberculin purified protein derivative (PPD). Antigen-specific T cell responses result in measurable induration at the injection site by 48-72 hours after injection, which indicates exposure to Mycobacterium antigens. However, a problem of sensitivity and specificity arises with regard to this test, and individuals vaccinated with BCG cannot be distinguished from infected individuals.
Macrophages play an important role not only in natural immunity or inflammatory responses but also in acquired immune responses, and the representative function is presenting antigens to T cells (antigen presentation). Macrophages receive protein antigens by phagocytosis, decompose them into small peptides (antigen processing), and bind the decomposed peptides to their MHCs, to promote the activation of T cells again on the cell surface. Also, macrophages act as the principal effector cells that indicate immunological action in cell-mediated immune responses and humoral immune responses, as well as having the function of suggesting antigens required to initiate immune responses. Macrophages activated by T cells perform the function of removing antigens from a delayed-type hypersensitivity reaction, and macrophages have the function of removing antigens bound by antibodies, with phagocytosis.
The inventors of the present invention confirmed that Mycobacterium tuberculosis disturbs the M1 polarization of macrophages by secreting pathogenic factors and confirmed therefrom the inhibitory efficacy of survival or proliferation of Mycobacterium tuberculosis by inducing polarization of macrophages, thereby completing the present invention.